Cutaneous angiosarcoma is a life-threatening tumor that is resistant to conventional therapies. The therapeutic effects of Sendai virus particles (hemagglutinating virus of Japan envelope: HVJ-E) carrying IL-2 gene (HVJ-E/IL-2) were examined in a mouse model of angiosarcoma. Intra-tumoral injection of HVJ-E/IL-2 effectively inhibited the growth of angiosarcoma cells (ISOS-1) inoculated in mice and improved tumor-free rates. HVJ-E/IL-2 stimulated local accumulation of CD8 (+) T cells and NK cells and reduced regulatory T cells in regional lymph nodes. Notably, the prevalence of myeloid-derived suppressor cells was lower in HVJ-E/IL-2-treated mice than in HVJ-E-treated mice. HVJ-E/IL-2 treatment promoted IFN-γ production from CD8 (+) T cells in response to tumor cells, more significantly than HVJ-E treatment. Greatly improved tumor-free rates were obtained when sunitinib, a tyrosine kinase inhibitor, was administered in combination with HVJ-E/IL-2. Immunogene therapy with HVJ-E/IL-2 with or without sunitinib could be a promising therapeutic option for cutaneous angiosarcoma.
Keywords: BMDC; Bone marrow-derived dendritic cells; DCs; Dendritic cells; HVJ-E; HVJ-E carrying IL-2 gene; HVJ-E carrying pVAX1 plasmid; HVJ-E/IL-2; HVJ-E/pVAX1; Hemagglutinating virus of Japan envelope; ISOS-1 cells; ISOS-1 cells fused with HVJ-E; ISOS-1/HVJ; MDSC; Myeloid-derived suppressor cells; Regulatory T cells; S.D; Standard deviations; Sunitinib; TILs; Tregs; Tumor infiltrating lymphocytes.
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